Increased fluid intake for the prevention of urinary tract infection in adults and children in all settings: a systematic review.

BACKGROUND: Non-antibiotic interventions for urinary tract infection (UTI) prevention have been investigated as a strategy to reduce antibiotic prescribing for UTI and subsequent antibiotic resistance. Increased hydration is widely advocated for preventing UTI; however, evidence for its effectiveness is unknown. AIM: To systematically review the published literature on the effectiveness of increased fluid intake as a preventive intervention for UTI in adults and children in any setting. METHODS: Five electronic databases were searched from inception to February 2019 to identify published randomized controlled trials (RCTs) and quasi-experimental studies evaluating the effectiveness of high (≥1.5 L/24 h) versus normal/low (<1.5 L/24 h) fluid intake for UTI prevention. The outcome was UTI incidence. Risk of bias was assessed using the Cochrane Collaboration's tool. Due to the small number of studies identified, meta-analysis was not possible. Hence a narrative synthesis was undertaken. FINDINGS: Of the 2822 potentially relevant papers, two were eligible for inclusion: an RCT (individual randomization) and a cluster-RCT. Both studies differed regarding participants, setting, sample size, UTI definition, and intervention. The RCT was assessed as having a low risk of bias whereas the cluster-RCT had a high risk of bias. Only the RCT, which included healthy premenopausal women visiting primary care clinics, demonstrated statistical significance for the effect of high fluid intake for UTI prevention. CONCLUSION: The lack of enough adequately powered and robust RCTs highlights the need for further research on the effectiveness of this intervention for UTI prevention.

An overview of the safety pharmacology society strategic plan.

Safety Pharmacology studies are conducted to characterize the confidence by which biologically active new chemical entities (NCE) may be anticipated as safe. Non-clinical safety pharmacology studies aim to detect and characterize potentially undesirable pharmacodynamic activities using an array of in silico, in vitro and in vivo animal models. While a broad spectrum of methodological innovation and advancement of the science occurs within the Safety Pharmacology Society, the society also focuses on partnerships with health authorities and technology providers and facilitates interaction with organizations of common interest such as pharmacology, physiology, neuroscience, cardiology and toxicology. Education remains a primary emphasis for the society through content derived from regional and annual meetings, webinars and publication of its works it seeks to inform the general scientific and regulatory community. In considering the future of safety pharmacology the society has developed a strategy to successfully navigate forward and not be mired in stagnation of the discipline. Strategy can be defined in numerous ways but generally involves establishing and setting goals, determining what actions are needed to achieve those goals, and mobilizing resources within the society to accomplish the actions. The discipline remains in rapid evolution and its coverage is certain to expand to provide better guidance for more systems in the next few years. This overview from the Safety Pharmacology Society will outline the strategic plan from 2016 to 2018 and beyond and provide insight into the future of the discipline which builds upon a previous strategic plan established in 2009.

Development and evaluation of a website for surveillance of healthcare-associated urinary tract infections in Australia.

Phase II of the Surveillance to Reduce Urinary Tract Infections project piloted a website for point prevalence surveys of healthcare-associated (HAUTI) and catheter-associated urinary tract infection in Australian hospitals and aged care homes. This report describes development and evaluation of the website for online data collection. Evaluation findings from 38 data collectors indicated that most respondents found website registration and web form use easy (N = 22; 58% and N = 16; 43%, respectively). The need for improved computer literacy skills and automated data systems were highlighted. This study demonstrated a novel approach for Australian HAUTI data collection; however, refinements are needed before national roll-out.

Systematic review and meta-analysis of the effectiveness of antiseptic agents for meatal cleaning in the prevention of catheter-associated urinary tract infections.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are among the most common healthcare-associated infections. Antiseptic cleaning of the meatal area before and during catheter use may reduce the risk of CAUTIs. AIM: To undertake a systematic review of the literature and meta-analysis of studies investigating the effectiveness of antiseptic cleaning before urinary catheter insertion and during catheter use for prevention of CAUTIs. METHODS: Electronic databases were searched to identify randomized controlled trials. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and compared across intervention and control groups using DerSimonian-Laird random-effects model. Subgroup analyses were performed. Heterogeneity was estimated using the I2 statistic. FINDINGS: In total, 2665 potential papers were identified; of these, 14 studies were eligible for inclusion. There was no difference in the incidence of CAUTIs when comparing antiseptic and non-antiseptic agents (pooled OR 0.90, 95% CI 0.73-1.10; P=0.31), or when comparing different agents: povidone-iodine vs routine care; povidone-iodine vs soap and water; chlorhexidine vs water; povidone-iodine vs saline; povidone-iodine vs water; and green soap and water vs routine care (P>0.05 for all). Comparison of an antibacterial agent with routine care indicated near significance (P=0.06). There was no evidence of heterogeneity (I2=0%; P>0.05). Subgroup analyses showed no difference in the incidence of CAUTIs in terms of country, setting, risk of bias, sex and frequency of administration. CONCLUSIONS: There were no differences in CAUTI rates, although methodological issues hamper generalizability of this finding. Antibacterial agents may prove to be significant in a well-conducted study. The present results provide good evidence to inform infection control guidelines in catheter management.

Analysis of microscopic parameters of single-particle trajectories in neurons.

We performed a comparative study of the statistical uncertainties that arise when calculating the velocity and diffusion coefficients from single-particle trajectories. We show that a method where particle mean displacement is used to calculate velocity and mean square fluctuation is used to calculate diffusion coefficient offers greater accuracy than analysis of time-dependent mean square displacement. Our assessment of the performance of the two analysis strategies is conducted in two ways. First, we apply each of the methods to simulated trajectories where each parameter term is known. Second, we analyze the motion of previously uncharacterized EphB2 receptors in the membrane of hippocampal neurons. We find that EphB2 receptors display different types of motion mode and transition between these modes. We present our data as a distribution of microscopic diffusion coefficients for each particle trajectory, which we refer to as partial distributions. Partial distributions are summed to form a cumulative distribution of diffusion coefficients for EphB2 receptors in hippocampal neurons. The structure and interpretation of the EphB2 cumulative distribution are discussed.

High-efficiency, room-temperature nanosecond Yb:YAG laser.

Yb(3+)-doped gain media offer favorable properties for diode-pumped laser amplifiers for high-energy ns-pulses. To reach high optical-to-optical conversion efficiencies at room temperature however, very high and often impractical fluences are required both for pumping and extraction. Low temperature operation offers a solution, but the required cryogenic cooling systems add considerable complexity, bulkiness and cost. Multi-passing both pump and extraction beams through the gain medium is an alternative approach to overcome efficiency limitations at room temperature. In this article we present numerical and experimental results to this effect.We demonstrated ns-pulse output from a diode-pumped Yb:YAG amplifier at an energy of 566 mJ and an optical-to-optical efficiency of 20%, which is almost a doubling of the efficiency achieved with ns-lasers employing Yb(3+)-doped gain media at this energy level.

International Life Sciences Institute (Health and Environmental Sciences Institute, HESI) initiative on moving towards better predictors of drug-induced torsades de pointes.

Knowledge of the cardiac safety of emerging new drugs is an important aspect of assuring the expeditious advancement of the best candidates targeted at unmet medical needs while also assuring the safety of clinical trial subjects or patients. Present methodologies for assessing drug-induced torsades de pointes (TdP) are woefully inadequate in terms of their specificity to select pharmaceutical agents, which are human arrhythmia toxicants. Thus, the critical challenge in the pharmaceutical industry today is to identify experimental models, composite strategies, or biomarkers of cardiac risk that can distinguish a drug, which prolongs cardiac ventricular repolarization, but is not proarrhythmic, from one that prolongs the QT interval and leads to TdP. To that end, the HESI Proarrhythmia Models Project Committee recognized that there was little practical understanding of the relationship between drug effects on cardiac ventricular repolarization and the rare clinical event of TdP. It was on that basis that a workshop was convened in Virginia, USA at which four topics were introduced by invited subject matter experts in the following fields: Molecular and Cellular Biology Underlying TdP, Dynamics of Periodicity, Models of TdP Proarrhythmia, and Key Considerations for Demonstrating Utility of Pre-Clinical Models. Contained in this special issue of the British Journal of Pharmacology are reports from each of the presenters that set out the background and key areas of discussion in each of these topic areas. Based on this information, the scientific community is encouraged to consider the ideas advanced in this workshop and to contribute to these important areas of investigations over the next several years.

The lathyrus toxin, beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (ODAP), and homocysteic acid sensitize CA1 pyramidal neurons to cystine and L-2-amino-6-phosphonohexanoic acid.

A brief exposure of hippocampal slices to L-quisqualic acid (QUIS) sensitizes CA1 pyramidal neurons 30- to 250-fold to depolarization by certain excitatory amino acids analogues, e.g., L-2-amino-6-phosphonohexanoic acid (L-AP6), and by the endogenous compound, L-cystine. This phenomenon has been termed QUIS sensitization. A mechanism similar to that previously described for QUIS neurotoxicity has been proposed to describe QUIS sensitization. Specifically, QUIS has been shown to be sequestered into GABAergic interneurons by the System x(c)(-) and subsequently released by heteroexchange with cystine or L-AP6, resulting in activation of non-NMDA receptors. We now report two additional neurotoxins, the Lathyrus excitotoxin, beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (ODAP), and the endogenous compound, L-homocysteic acid (HCA), sensitize CA1 hippocampal neurons >50-fold to L-AP6 and >10-fold to cystine in a manner similar to QUIS. While the cystine- or L-AP6-mediated depolarization can be inhibited by the non-NMDA receptor antagonist CNQX in ODAP- or QUIS-sensitized slices, the NMDA antagonist D-AP5 inhibits depolarization by cystine or L-AP6 in HCA-sensitized slices. Thus, HCA is the first identified NMDA agonist that induces phosphonate or cystine sensitization. Like QUIS sensitization, the sensitization evoked by either ODAP or HCA can be reversed by a subsequent exposure to 2 mM alpha-aminoadipic acid. Finally, we have demonstrated that there is a correlation between the potency of inducers for triggering phosphonate or cystine sensitivity and their affinities for System x(c)(-) and either the non-NMDA or NMDA receptor. Thus, the results of this study support our previous model of QUIS sensitization and have important implications for the mechanisms of neurotoxicity, neurolathyrism and hyperhomocystinemia.

L-Quisqualic acid transport into hippocampal neurons by a cystine-sensitive carrier is required for the induction of quisqualate sensitization.

A brief exposure of hippocampal slices to L-quisqualic acid sensitizes CA1 pyramidal neurons 30-250-fold to depolarization by two classes of excitatory amino acid analogues: (1) those whose depolarizing effects are rapidly terminated following washout, e.g. L-2-amino-4-phosphonobutanoic acid (L-AP4) and L-2-amino-6-phosphonohexanoic acid (L-AP6) and (2) those whose depolarizing effects persist following washout, e.g. L-aspartate-beta-hydroxamate (L-AbetaH). This process has been termed quisqualate sensitization. In this study we directly examine the role of amino acid transport systems in the induction of quisqualate sensitization. We report that L-quisqualate is a low-affinity substrate (K(M)=0.54 mM) for a high capacity (V(max)=0.9 nmol (mg protein)(-1) min(-1)) Na(+)-dependent transport system(s) and a high-affinity substrate (K(M)=0.033 mM) for a low-capacity (V(max)=0.051 nmol (mg protein)(-1) min(-1)) transporter with properties similar to the cystine/glutamate exchange carrier, System x(c-). We present evidence that suggests that System x(c-) participates in quisqualate sensitization. First, simultaneous application of L-quisqualate and inhibitors of System x(c-), but not inhibitors of Na(+)-dependent glutamate transporters, prevents the subsequent sensitization of hippocampal neurons to phosphonates or L-AbetaH. Second, L-quisqualic acid only sensitizes hippocampal neurons to other substrates of System x(c-), including cystine. Third, immunocytochemical analysis of L-quisqualate uptake demonstrates that only inhibitors of System x(c-) inhibit the highly concentrative uptake of L-quisqualate into a widely dispersed group of GABAergic hippocampal interneurons. We conclude that quisqualate sensitization is a direct consequence of the unique interaction of various excitatory amino acids, namely L-quisqualate, cystine, and phosphonates, with the exchange carrier, System x(c-). Therefore, the results of this study have important implications for the mechanism by which L-quisqualate, and other substrates of this transporter which are also excitatory amino acid agonists (such as glutamate and beta-N-oxalyl-L-alpha,beta-diaminopropionic acid, beta-L-ODAP) may trigger neurotoxicity.

Test-retest reliability and internal consistency of a variety of measures of dietary restraint and body concerns in a sample of adolescent girls.

OBJECTIVE: Internal consistency and test-retest reliability were examined in a variety of measures relating to body concerns and dieting and eating behaviors. METHOD: Grade 9 females (n = 363) from nine schools completed questionnaires with the aid of a definitions glossary at Time 1, including the five subscales of the Eating Attitudes Test, the Dutch Eating Behavior Questionnaire-Restraint scale, a variety of measures of current size and ideal size (self, parents) based on the Body Figure Rating Questionnaire, the Appearance Evaluation and Appearance Orientation subscales of the Multidimensional Body Self-Rating Questionnaire, and the Weight Loss Behaviors Scale. Four to 5 weeks later, 164 girls completed the questionnaires again. RESULTS AND DISCUSSION: Findings indicated adequate internal consistency and high test-retest correlations for all measures. Some measures, particularly those related to body size and dietary restraint, showed a slight increase in group means over time.

Plague as a biological weapon: medical and public health management. Working Group on Civilian Biodefense.

OBJECTIVE: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals following the use of plague as a biological weapon against a civilian population. PARTICIPANTS: The working group included 25 representatives from major academic medical centers and research, government, military, public health, and emergency management institutions and agencies. EVIDENCE: MEDLINE databases were searched from January 1966 to June 1998 for the Medical Subject Headings plague, Yersinia pestis, biological weapon, biological terrorism, biological warfare, and biowarfare. Review of the bibliographies of the references identified by this search led to subsequent identification of relevant references published prior to 1966. In addition, participants identified other unpublished references and sources. Additional MEDLINE searches were conducted through January 2000. CONSENSUS PROCESS: The first draft of the consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group was convened to review drafts of the document in October 1998 and May 1999. The final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members. CONCLUSIONS: An aerosolized plague weapon could cause fever, cough, chest pain, and hemoptysis with signs consistent with severe pneumonia 1 to 6 days after exposure. Rapid evolution of disease would occur in the 2 to 4 days after symptom onset and would lead to septic shock with high mortality without early treatment. Early treatment and prophylaxis with streptomycin or gentamicin or the tetracycline or fluoroquinolone classes of antimicrobials would be advised.

Nightingale II: nursing leaders re-membering community.

As the health care field moves into the 21st century, the discipline is moving into new forms of service and leadership. This article presents a view of nursing leadership from the vantage point of community. Values, beliefs, and the changing roles of nursing leadership in creation of new order are examined along with skills and capacities necessary to accomplish the task at hand.

Cyclobutane quisqualic acid analogues as selective mGluR5a metabotropic glutamic acid receptor ligands.

The conformationally constrained cyclobutane analogues of quisqualic acid (Z)- and (E)-1-amino-3-[2'-(3',5'-dioxo-1',2', 4'-oxadiazolidinyl)]cyclobutane-1-carboxylic acid, compounds 2 and 3, respectively, were synthesized. Both 2 and 3 stimulated phosphoinositide (PI) hydrolysis in the hippocampus with EC50 values of 18 +/- 6 and 53 +/- 19 microM, respectively. Neither analogue stimulated PI hydrolysis in the cerebellum. The effects of 2 and 3 were also examined in BHK cells which expressed either mGluR1a or mGluR5a receptors. Compounds 2 and 3 stimulated PI hydrolysis in cells expressing mGluR5a but not in those cells expressing mGluR1a. The EC50 value for 2 was 11 +/- 4 microM, while that for 3 was 49 +/- 25 microM. Both 2 and 3 did not show any significant effect on cells expressing the mGluR2 and mGluR4a receptors. In addition, neither compound blocked [3H]glutamic acid uptake into synaptosomal membranes, and neither compound was able to produce the QUIS effect as does quisqualic acid. This pharmacological profile indicates that 2 and 3 are selective ligands for the mGluR5a metabotropic glutamic acid receptor.

Profiles of leadership: a dialogue with two nursing revolutionaries.

Rebels break the rules and revolutionaries rewrite them because the old rules are no longer adequate. These revolutionary leaders examine their life journeys and highlight issues and events that prepared them for nontraditional nursing roles; that of consultant and CEO. Patterns of thought and behavior nested within their stories provide a rich map for the contemporary nurse seeking to expand their view of the health care landscape.